rTMS for Neuropathic Pain After Spinal Cord Injury

Overseen By Melanie H Vergeer, MSc

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Calgary

Disqualifiers: Pacemaker, Metallic implant, Seizure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 21

Duration: 4 weeks

10 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Repetitive Transcranial Magnetic Stimulation (rTMS) for neuropathic pain after spinal cord injury?

Research suggests that repetitive transcranial magnetic stimulation (rTMS) can help relieve neuropathic pain after a spinal cord injury. Some studies have shown that rTMS applied to specific brain areas can reduce pain, although results can vary, and the best way to use this treatment is still being studied. ^{1 2 3 4 5}

Is repetitive transcranial magnetic stimulation (rTMS) safe for humans?

Repetitive transcranial magnetic stimulation (rTMS) is generally considered safe for humans, as it is a non-invasive treatment that has been studied for various types of neuropathic pain, including those related to spinal cord injury. ^{2 3 4 5 6}

How is the treatment rTMS different from other treatments for neuropathic pain after spinal cord injury?

Repetitive Transcranial Magnetic Stimulation (rTMS) is unique because it uses magnetic fields to stimulate specific areas of the brain, particularly the motor cortex, to relieve pain. Unlike medications, it is a non-invasive procedure that can provide pain relief without the need for surgery or drugs, and it has been shown to be effective even when other treatments have failed. ^{4 5 7 8 9}

What is the purpose of this trial?

This study aims to determine if repetitive transcranial magnetic stimulation (rTMS) can improve pain symptomology in adults with neuropathic pain (NP) following a spinal cord injury (SCI).

Research Team

Chantel T Debert, MD MSc FRCPC CSCN

Principal Investigator

University of Calgary

Eligibility Criteria

This trial is for adults aged 18-75 with neuropathic pain lasting at least 3 months due to a spinal cord injury. Candidates must not have other conditions causing the pain, no prior TMS therapy, and no contraindications like pacemakers, metal implants in the head, seizures, severe psychiatric disorders, or uncontrolled major diseases.

Inclusion Criteria

I have been diagnosed with nerve pain for at least 3 months.

I have a spinal cord injury diagnosed by a doctor.

My pain is only due to my current health condition.

Exclusion Criteria

I have previously undergone TMS therapy.

I do not have a pacemaker, metal implants, serious brain issues, seizures, severe mental health issues, recent suicide attempts, liver or kidney disease, cancer, uncontrolled high blood pressure or diabetes, and I am not pregnant.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo high frequency rTMS sessions 5 days a week for 4 weeks

4 weeks

20 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

Assessments at 1 month and 3 months post-treatment

Treatment Details

Interventions

• Repetitive Transcranial Magnetic Stimulation (rTMS)

Trial Overview The study tests whether repetitive Transcranial Magnetic Stimulation (rTMS) can relieve neuropathic pain in individuals who've suffered a spinal cord injury. rTMS is a non-invasive procedure that uses magnetic fields to stimulate nerve cells in the brain.

Participant Groups

Group I: Repetitive Transcranial Magnetic Stimulation (rTMS) Experimental Treatment 1 Intervention

Participants will undergo high frequency rTMS sessions 5 days a week for 4 weeks (20 treatments total). Treatment intensity will be applied at 100-120% of the participant's resting motor threshold. The neurostimulation protocol will be 10 trains of 60 pulses (600 pulses total) at a frequency of 10 Hz, with inter-train interval of 45-seconds. The rTMS will be administered to the dorsolateral prefrontal cortex (DLPFC) which will be located using Montreal Neurologic Institute (MNI) coordinates (-50, 30, 36) on a standardized brain. Participants will be seated in a comfortable chair or their wheelchair for each rTMS session.

Repetitive Transcranial Magnetic Stimulation (rTMS) is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as rTMS for:

• Depression
• Smoking cessation

Approved in European Union as rTMS for:

• Depression

Approved in Canada as rTMS for:

• Depression

Approved in Japan as rTMS for:

• Depression

Who Is Running the Clinical Trial?

University of Calgary

Lead Sponsor

Trials

827

Recruited

902,000+

Findings from Research

High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) is effective in reducing neuropathic pain, with significant pain relief observed after just one and five treatment sessions, based on a meta-analysis of 25 studies involving 589 patients.

The analgesic effects of HF-rTMS can last for at least one month after five sessions, indicating its potential for long-term pain management in neuropathic pain patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High Frequency Repetitive Transcranial Magnetic Stimulation Therapy For Chronic Neuropathic Pain: A Meta-analysis. Jin, Y., Xing, G., Li, G., et al.[2018]

In a study involving 17 patients with spinal cord injury and chronic neuropathic pain, repetitive transcranial magnetic stimulation (rTMS) did not show a significant advantage over sham treatment in reducing pain levels, indicating that its analgesic effect may not be superior to placebo.

Despite the lack of significant difference compared to sham treatment, rTMS did provide encouraging pain relief at 10 days and 6 weeks post-treatment, suggesting potential for further research with larger sample sizes to explore its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of repetitive transcranial magnetic stimulation on refractory neuropathic pain in spinal cord injury. Yılmaz, B., Kesikburun, S., Yaşar, E., et al.[2021]

A study involving 66 patients with neuropathic pain showed that high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) targeting the specific pain region using navigation techniques provided significant pain relief, particularly for upper and lower limb pain.

The pain relief from navigated rTMS lasted for one week, indicating that navigation may enhance the efficacy of rTMS compared to traditional non-navigated methods, although it was less effective for facial or diffuse pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analgesic effects of navigated motor cortex rTMS in patients with chronic neuropathic pain. Ayache, SS., Ahdab, R., Chalah, MA., et al.[2022]

Motor cortex stimulation can effectively control neuropathic pain in many patients, and repetitive transcranial magnetic stimulation (rTMS) can provide analgesic effects as well.

In a reported case, a woman with drug-resistant peripheral pain experienced 16 months of pain relief from monthly rTMS sessions before receiving a surgical cortical stimulator, highlighting rTMS as a valuable interim treatment before surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuropathic pain controlled for more than a year by monthly sessions of repetitive transcranial magnetic stimulation of the motor cortex. Lefaucheur, JP., Drouot, X., Ménard-Lefaucheur, I., et al.[2011]

Repetitive transcranial magnetic stimulation (rTMS) applied to the M1/S1 cortex significantly lowers μ-opioid receptor availability, indicating the release of endogenous opioids in various brain regions associated with pain processing, which may contribute to its pain-relieving effects.

Despite the activation of the endogenous opioid system, rTMS did not change thermal pain thresholds or sensory discrimination of painful stimuli, suggesting that while rTMS enhances opioid-mediated inhibition, it does not alter the perception of pain intensity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurotransmitters behind pain relief with transcranial magnetic stimulation - positron emission tomography evidence for release of endogenous opioids. Lamusuo, S., Hirvonen, J., Lindholm, P., et al.[2018]

References

1. United States pubmed.ncbi.nlm.nih.gov

Effect of non-invasive brain stimulation on neuropathic pain following spinal cord injury: A systematic review and meta-analysis. [2022]

2. Scotland pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation accuracy as a spinal cord stimulation outcome predictor in patients with neuropathic pain. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

High Frequency Repetitive Transcranial Magnetic Stimulation Therapy For Chronic Neuropathic Pain: A Meta-analysis. [2018]

4. England pubmed.ncbi.nlm.nih.gov

Analgesic Effects of Directed Repetitive Transcranial Magnetic Stimulation in Acute Neuropathic Pain After Spinal Cord Injury. [2022]

5. England pubmed.ncbi.nlm.nih.gov

The effect of repetitive transcranial magnetic stimulation on refractory neuropathic pain in spinal cord injury. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Longlasting antalgic effects of daily sessions of repetitive transcranial magnetic stimulation in central and peripheral neuropathic pain. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Analgesic effects of navigated motor cortex rTMS in patients with chronic neuropathic pain. [2022]

8. France pubmed.ncbi.nlm.nih.gov

Neuropathic pain controlled for more than a year by monthly sessions of repetitive transcranial magnetic stimulation of the motor cortex. [2011]

9. England pubmed.ncbi.nlm.nih.gov

Neurotransmitters behind pain relief with transcranial magnetic stimulation - positron emission tomography evidence for release of endogenous opioids. [2018]